{"id":"https://openalex.org/W4396591263","doi":"https://doi.org/10.1158/1538-7445.sabcs23-po3-26-09","title":"Abstract PO3-26-09: A novel class of RNR inhibitors that induces genomic instability and breast cancer cell death without inducing overt toxicities","display_name":"Abstract PO3-26-09: A novel class of RNR inhibitors that induces genomic instability and breast cancer cell death without inducing overt toxicities","publication_year":2024,"publication_date":"2024-05-02","ids":{"openalex":"https://openalex.org/W4396591263","doi":"https://doi.org/10.1158/1538-7445.sabcs23-po3-26-09"},"language":"en","primary_location":{"id":"doi:10.1158/1538-7445.sabcs23-po3-26-09","doi":"https://doi.org/10.1158/1538-7445.sabcs23-po3-26-09","is_oa":false,"landing_page_url":"http://dx.doi.org/10.1158/1538-7445.sabcs23-po3-26-09","pdf_url":null,"source":{"id":"https://openalex.org/S168522863","display_name":"Cancer Research","issn_l":"0008-5472","issn":["0008-5472","1538-7445"],"is_oa":false,"is_in_doaj":false,"is_core":true,"listed_in":["anvur-scientific","cwts-core","dongbi-a","doyens","jufo-3","ki-jl-3","medline","norway-2","poland-200","russia-white-list-1","vabb-shw"],"host_organization":"https://openalex.org/P4310320273","host_organization_name":"American Association for Cancer Research","host_organization_lineage":["https://openalex.org/P4310320273"],"host_organization_lineage_names":["American Association for Cancer Research"],"type":"journal"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Cancer Research","raw_type":"journal-article"},"volume":null,"type":"conference-abstract","is_traditional":false,"indexed_in":["crossref"],"open_access":{"is_oa":false,"oa_status":"closed","oa_url":null,"any_repository_has_fulltext":false},"authorships":[{"author_position":"first","author":{"id":"https://openalex.org/A5017971192","display_name":"Taylor Baker","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I58956616","display_name":"Case Western Reserve University","ror":"https://ror.org/051fd9666","country_code":"US","type":"education","lineage":["https://openalex.org/I58956616"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Taylor Baker","raw_affiliation_strings":["1Case Western Reserve University;"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"1Case Western Reserve University;","institution_ids":["https://openalex.org/I58956616"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5035038770","display_name":"Kristen L. Weber-Bonk","orcid":"https://orcid.org/0000-0003-2175-5800","observed_orcids":["https://orcid.org/0000-0003-2175-5800"]},"institutions":[{"id":"https://openalex.org/I1316902750","display_name":"Cleveland Clinic","ror":"https://ror.org/03xjacd83","country_code":"US","type":"healthcare","lineage":["https://openalex.org/I1316902750"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Kristen Weber-Bonk","raw_affiliation_strings":["2Cleveland Clinic"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"2Cleveland Clinic","institution_ids":["https://openalex.org/I1316902750"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5022470629","display_name":"Wei Huang","orcid":"https://orcid.org/0000-0003-2097-8148","observed_orcids":["https://orcid.org/0000-0003-2097-8148"]},"institutions":[{"id":"https://openalex.org/I58956616","display_name":"Case Western Reserve University","ror":"https://ror.org/051fd9666","country_code":"US","type":"education","lineage":["https://openalex.org/I58956616"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Wei Huang","raw_affiliation_strings":["1Case Western Reserve University;"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"1Case Western Reserve University;","institution_ids":["https://openalex.org/I58956616"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5002785674","display_name":"Derek J. Taylor","orcid":"https://orcid.org/0000-0001-9932-1856","observed_orcids":["https://orcid.org/0000-0001-9932-1856"]},"institutions":[{"id":"https://openalex.org/I58956616","display_name":"Case Western Reserve University","ror":"https://ror.org/051fd9666","country_code":"US","type":"education","lineage":["https://openalex.org/I58956616"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Derek Taylor","raw_affiliation_strings":["1Case Western Reserve University;"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"1Case Western Reserve University;","institution_ids":["https://openalex.org/I58956616"]}]},{"author_position":"last","author":{"id":"https://openalex.org/A5020136425","display_name":"Ruth A. Keri","orcid":"https://orcid.org/0000-0002-1640-3088","observed_orcids":["https://orcid.org/0000-0002-1640-3088"]},"institutions":[{"id":"https://openalex.org/I1316902750","display_name":"Cleveland Clinic","ror":"https://ror.org/03xjacd83","country_code":"US","type":"healthcare","lineage":["https://openalex.org/I1316902750"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Ruth Keri","raw_affiliation_strings":["2Cleveland Clinic"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"2Cleveland Clinic","institution_ids":["https://openalex.org/I1316902750"]}]}],"institutions":[],"countries_distinct_count":1,"institutions_distinct_count":2,"corresponding_author_ids":[],"corresponding_institution_ids":[],"apc_list":null,"apc_paid":null,"fwci":null,"has_fulltext":false,"cited_by_count":0,"citation_normalized_percentile":null,"cited_by_percentile_year":null,"biblio":{"volume":"84","issue":"9_Supplement","first_page":"PO3","last_page":"26"},"is_retracted":false,"is_paratext":false,"is_xpac":false,"primary_topic":{"id":"https://openalex.org/T12827","display_name":"Biochemical and Molecular Research","score":0.4812000095844269,"subfield":{"id":"https://openalex.org/subfields/1312","display_name":"Molecular Biology"},"field":{"id":"https://openalex.org/fields/13","display_name":"Biochemistry, Genetics and Molecular Biology"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}},"topics":[{"id":"https://openalex.org/T12827","display_name":"Biochemical and Molecular Research","score":0.4812000095844269,"subfield":{"id":"https://openalex.org/subfields/1312","display_name":"Molecular Biology"},"field":{"id":"https://openalex.org/fields/13","display_name":"Biochemistry, Genetics and Molecular Biology"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}},{"id":"https://openalex.org/T11845","display_name":"Cancer therapeutics and mechanisms","score":0.09669999778270721,"subfield":{"id":"https://openalex.org/subfields/1312","display_name":"Molecular Biology"},"field":{"id":"https://openalex.org/fields/13","display_name":"Biochemistry, Genetics and Molecular Biology"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}},{"id":"https://openalex.org/T12356","display_name":"Bioactive Compounds and Antitumor Agents","score":0.09189999848604202,"subfield":{"id":"https://openalex.org/subfields/3005","display_name":"Toxicology"},"field":{"id":"https://openalex.org/fields/30","display_name":"Pharmacology, Toxicology and Pharmaceutics"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}}],"keywords":[{"id":"https://openalex.org/keywords/ribonucleotide-reductase-inhibitors","display_name":"ribonucleotide reductase inhibitors","score":0.9290000200271606},{"id":"https://openalex.org/keywords/rrm2","display_name":"RRM2","score":0.6679999828338623},{"id":"https://openalex.org/keywords/genomic-instability","display_name":"genomic instability","score":0.6129999756813049},{"id":"https://openalex.org/keywords/triple-negative-breast-cancer","display_name":"triple-negative breast cancer","score":0.796999990940094},{"id":"https://openalex.org/keywords/metastatic-breast-cancer","display_name":"metastatic breast cancer","score":0.8169999718666077},{"id":"https://openalex.org/keywords/dna-damage","display_name":"DNA damage","score":0.5870000123977661},{"id":"https://openalex.org/keywords/apoptosis","display_name":"apoptosis","score":0.5899999737739563},{"id":"https://openalex.org/keywords/senescence","display_name":"senescence","score":0.8999999761581421}],"concepts":[{"id":"https://openalex.org/C178169997","wikidata":"https://www.wikidata.org/wiki/Q2892636","display_name":"Genome instability","level":4,"score":0.7809884548187256},{"id":"https://openalex.org/C530470458","wikidata":"https://www.wikidata.org/wiki/Q128581","display_name":"Breast cancer","level":3,"score":0.6892380118370056},{"id":"https://openalex.org/C121608353","wikidata":"https://www.wikidata.org/wiki/Q12078","display_name":"Cancer","level":2,"score":0.6262906789779663},{"id":"https://openalex.org/C31573885","wikidata":"https://www.wikidata.org/wiki/Q304484","display_name":"Programmed cell death","level":3,"score":0.5430377125740051},{"id":"https://openalex.org/C502942594","wikidata":"https://www.wikidata.org/wiki/Q3421914","display_name":"Cancer research","level":1,"score":0.5000157356262207},{"id":"https://openalex.org/C86803240","wikidata":"https://www.wikidata.org/wiki/Q420","display_name":"Biology","level":0,"score":0.3856545686721802},{"id":"https://openalex.org/C71924100","wikidata":"https://www.wikidata.org/wiki/Q11190","display_name":"Medicine","level":0,"score":0.37729910016059875},{"id":"https://openalex.org/C126322002","wikidata":"https://www.wikidata.org/wiki/Q11180","display_name":"Internal medicine","level":1,"score":0.2873755097389221},{"id":"https://openalex.org/C54355233","wikidata":"https://www.wikidata.org/wiki/Q7162","display_name":"Genetics","level":1,"score":0.2601759135723114},{"id":"https://openalex.org/C190283241","wikidata":"https://www.wikidata.org/wiki/Q14599311","display_name":"Apoptosis","level":2,"score":0.1859249472618103},{"id":"https://openalex.org/C143425029","wikidata":"https://www.wikidata.org/wiki/Q5205747","display_name":"DNA damage","level":3,"score":0.13219213485717773},{"id":"https://openalex.org/C552990157","wikidata":"https://www.wikidata.org/wiki/Q7430","display_name":"DNA","level":2,"score":0.11686348915100098}],"mesh":[],"locations_count":1,"locations":[{"id":"doi:10.1158/1538-7445.sabcs23-po3-26-09","doi":"https://doi.org/10.1158/1538-7445.sabcs23-po3-26-09","is_oa":false,"landing_page_url":"http://dx.doi.org/10.1158/1538-7445.sabcs23-po3-26-09","pdf_url":null,"source":{"id":"https://openalex.org/S168522863","display_name":"Cancer Research","issn_l":"0008-5472","issn":["0008-5472","1538-7445"],"is_oa":false,"is_in_doaj":false,"is_core":true,"listed_in":["anvur-scientific","cwts-core","dongbi-a","doyens","jufo-3","ki-jl-3","medline","norway-2","poland-200","russia-white-list-1","vabb-shw"],"host_organization":"https://openalex.org/P4310320273","host_organization_name":"American Association for Cancer Research","host_organization_lineage":["https://openalex.org/P4310320273"],"host_organization_lineage_names":["American Association for Cancer Research"],"type":"journal"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Cancer Research","raw_type":"journal-article"}],"best_oa_location":null,"sustainable_development_goals":[{"display_name":"Good health and well-being","score":0.9763000011444092,"id":"https://metadata.un.org/sdg/3"}],"study_designs":[],"awards":[],"funders":[],"has_content":{"grobid_xml":false,"pdf":false},"content_urls":null,"referenced_works_count":0,"referenced_works":[],"related_works":["https://openalex.org/W2903149622","https://openalex.org/W3171949172","https://openalex.org/W4252520025","https://openalex.org/W2024465220","https://openalex.org/W2735479170","https://openalex.org/W4307860461","https://openalex.org/W2211440948","https://openalex.org/W2014286808","https://openalex.org/W4412635335","https://openalex.org/W2481050409"],"abstract_inverted_index":{"Abstract":[0],"Despite":[1],"the":[2,36,43,49,77,147,185,192,219,227,316,354,377,431],"development":[3],"of":[4,11,46,128,188,195,300,318,356,379,384,411,430],"screening":[5],"techniques":[6],"and":[7,54,100,157,176,218,263,266,274,285,329,343,367,394,418],"therapies,":[8],"nearly":[9],"30%":[10],"breast":[12,61,72,291,360,419],"cancers":[13,22],"progress":[14],"to":[15,83,103,146,190,247,254,270,325],"Stage":[16,85],"IV":[17,86],"metastatic":[18],"disease.":[19,87],"These":[20],"advanced":[21,71],"are":[23,347,363],"highly":[24],"proliferative,":[25],"engaging":[26],"in":[27,57,70,137,139,226,287,315],"ongoing":[28],"DNA":[29,105,220,272],"synthesis":[30],"that":[31,110,234,252,341,352,414],"requires":[32],"ribonucleotide":[33],"reductase":[34],"(RNR),":[35],"rate-limiting":[37],"enzyme":[38],"for":[39,142,358],"dNTP":[40],"synthesis.":[41],"RRM2,":[42],"small":[44],"subunit":[45],"RNR,":[47,196],"activates":[48],"enzyme,":[50],"increases":[51],"deoxynucleotide":[52],"pools,":[53],"is":[55,65,76,199],"overexpressed":[56],"many":[58],"cancers,":[59],"including":[60],"cancer.":[62,73,361],"Thus,":[63],"RNR":[64,80,114,148,159,237,350,372,385,412],"an":[66,138],"established":[67],"therapeutic":[68],"target":[69],"Currently,":[74],"gemcitabine":[75,92,326,357],"only":[78],"FDA-approved":[79],"inhibitor":[81,115],"used":[82,162],"treat":[84],"As":[88],"a":[89,111,126,240,381],"nucleoside":[90],"analog,":[91],"also":[93,211],"causes":[94,281],"severe":[95],"dose-limiting":[96],"toxicities":[97,426],"(i.e.":[98],"myelosuppression":[99],"hepatotoxicity)":[101],"due":[102],"off-target":[104,245],"replication":[106],"termination.":[107],"We":[108,362],"hypothesize":[109],"novel,":[112,348],"non-nucleoside,":[113],"may":[116],"overcome":[117,353],"these":[118,338],"limitations.":[119],"To":[120,151],"address":[121],"this,":[122],"we":[123,161],"developed":[124],"TMU27a,":[125],"derivative":[127],"naphthyl":[129],"salicylic":[130],"acyl":[131],"hydrazone":[132],"(NSAH),":[133],"which":[134],"was":[135],"identified":[136],"silico":[140],"screen":[141],"its":[143,344],"high-affinity":[144],"binding":[145,169,186,246,250,392],"catalytic":[149,193],"site.":[150],"measure":[152],"direct":[153],"interactions":[154,203],"between":[155,216],"TMU27a":[156,189,217,235,259,302,334,342,369],"purified":[158],"protein,":[160],"surface":[163],"plasmon":[164],"resonance,":[165],"revealing":[166],"on-target,":[167],"tight":[168],"(Kd":[170],"=":[171],"150":[172],"nM).":[173],"Unbiased":[174],"docking":[175,209],"molecular":[177],"dynamics":[178],"simulations":[179],"(using":[180],"lowest":[181,228],"energy":[182,229],"calculations)":[183],"predicted":[184],"sight":[187],"be":[191],"site":[194],"where":[197,368],"it":[198],"stabilized":[200],"through":[201,239,387],"extensive":[202],"formed":[204],"with":[205,376],"conserved":[206],"residues.":[207],"Preliminary":[208],"predictions":[210],"indicate":[212,340],"multiple":[213],"clash":[214],"sites":[215],"polymerase":[221],"lambda":[222],"nucleotide":[223,249],"pocket":[224],"even":[225],"pose":[230],"(unlike":[231],"gemcitabine),":[232],"suggesting":[233,311],"inhibits":[236],"activity":[238],"novel":[241,382,409],"mechanism":[242],"without":[243,307,423],"significant":[244,271],"other":[248],"proteins":[251],"contribute":[253],"toxicity.":[255,320],"Demonstrating":[256],"on-target":[257],"inhibition,":[258],"reduces":[260],"dATP":[261],"levels":[262],"induces":[264,415],"S":[265],"G2/M-phase":[267],"stalling,":[268],"leading":[269],"damage":[273,280],"chromosomal":[275],"instability.":[276],"This":[277],"excessive":[278],"genomic":[279,416],"growth":[282,306],"repression,":[283],"apoptosis,":[284],"senescence":[286],"several":[288],"triple":[289],"negative":[290],"cancer":[292,420],"(TNBC)":[293],"cell":[294,332,421],"lines.":[295],"In":[296],"xenograft":[297],"mouse":[298,309],"models":[299],"TNBC,":[301],"fully":[303],"suppressed":[304],"tumor":[305],"impacting":[308],"weight,":[310],"strong":[312],"drug":[313,389],"efficacy":[314],"absence":[317],"overt":[319,425],"Moreover,":[321],"while":[322],"short-term":[323],"exposure":[324],"suppresses":[327],"red":[328],"white":[330],"blood":[331],"populations,":[333],"does":[335],"not.":[336],"Together,":[337],"data":[339],"potential":[345],"analogs":[346],"non-toxic":[349],"inhibitors":[351,386,413],"limitations":[355],"treating":[359],"currently":[364],"investigating":[365],"how":[366],"binds":[370],"human":[371],"using":[373],"cryo-electron":[374],"microscopy":[375],"goal":[378],"generating":[380],"class":[383,410],"structure-based":[388],"design,":[390],"improving":[391],"affinity":[393],"selectivity.":[395],"Citation":[396],"Format:":[397],"Taylor":[398],"Baker,":[399],"Kristen":[400],"Weber-Bonk,":[401],"Wei":[402],"Huang,":[403],"Derek":[404],"Taylor,":[405],"Ruth":[406],"Keri.":[407],"A":[408],"instability":[417],"death":[422],"inducing":[424],"[abstract].":[427],"In:":[428],"Proceedings":[429],"2023":[432,438],"San":[433,441],"Antonio":[434],"Breast":[435],"Cancer":[436,447],"Symposium;":[437],"Dec":[439],"5-9;":[440],"Antonio,":[442],"TX.":[443],"Philadelphia":[444],"(PA):":[445],"AACR;":[446],"Res":[448],"2024;84(9":[449],"Suppl):Abstract":[450],"nr":[451],"PO3-26-09.":[452]},"counts_by_year":[],"updated_date":"2026-07-14T23:27:15.235271","created_date":"2024-05-03T00:00:00"}